Acta Pharm. 57 (2007) 441-450

full paper

Original research paper

Ketorolac-dextran conjugates: Synthesis, in vitro and in vivo evaluation

SAVITA VYAS, PIYUSH TRIVEDI and SUBHASH CHANDRA CHATURVEDI

vyassavita@yahoo.com

Department of Pharmacology, M. G. M. Medical College, A. B. Road, Indore-452001, India

Shri. G. S. Institute of Technology and Science, Department of Pharmacy, 23 Park Road, Indore-452003, India

School of Pharmacy, DAVV, Indore-452017, India

Accepted September 10, 2007

Ketorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. In vitro hydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. In vivo biological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.

Keywords: ketorolac-dextran conjugates, dextran carrier, NSAIDs